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基于表观遗传的摄取型药物转运体表达调控是肿瘤耐药干预的新途径 预览

Epigenetics-based regulation of uptake drug transporter expression is a new approach for cancer drug resistance intervention
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摘要 肿瘤耐药是临床化疗效果不佳的关键因素,其中药物代谢酶和药物转运体表达异常引起肿瘤细胞中药物浓度下降是导致耐药的重要原因之一。文章从药物代谢酶和转运体与肿瘤耐药、药物表观遗传学与耐药、肾癌耐药的潜在靶标OCT2等方面分析了肿瘤摄取转运体表达异常的机制,提出通过表观遗传机制调节肿瘤细胞中摄取型药物转运体表达是逆转肿瘤耐药的新途径。 Drug resistance is a key factor for poor clinical efficacy of chemotherapy. One of the important reasons for drug resistance is the abnormal expression of drug metabolizing enzymes and drug transporters,which results in the decrease of drug concentration in cancer cells. In this paper,the mechanism of abnormal uptake transporter expression in tumors is analyzed from aspects of drug metabolism enzymes and transporters and tumor drug resistance,drug epigenetics and drug resistance,and potential targets of renal cancer drug resistance,such as OCT2. It is proposed that the regulation of uptake drug transporter expression in tumors by epigenetic mechanism is a new way to reverse drug resistance in tumors.
作者 余露山 曾苏 YU Lu-shan;ZENG Su(Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, ZhejiangUniversity,Hangzhou 310058,Zhejiang,China)
出处 《医学研究生学报》 CAS 北大核心 2019年第5期449-454,共6页 Journal of Medical Postgraduates
基金 国家自然科学基金(81773817).
关键词 肿瘤耐药 表观遗传 药物转运体 DNA甲基化 drug resistance epigenetics drug transporters DNA methylation
作者简介 通信作者:曾苏,药学博士,浙江大学药学院教授、学术委员会主任、药物代谢和药物分析研究所所长。从事药物代谢动力学、药品质量控制等研究。现任国家药典委员会委员、国家药品审评专家、中国药学会理事、中国药理学会分析药理学专业委员会主任和药物代谢专业委员会副主任、中国生物医药技术协会药物分析技术分会副主任、中国仪器仪表学会药物质量分析与过程控制分会副理事长、中国药学会应用药理专业委员会委员、中国化学会手性化学专业委员会委员、浙江省药学会副理事长。J Pharm Anal、J Chin Pharm Sic 副主编, Drug Metab Dispo、Phytomed、Curr Pharm Anal等杂志编委。国家杰出青年基金获得者和全国优秀教师奖章获得者、享受国务院政府特殊津贴、入选国家“百千万人才工程。主持国家自然科学基金重点项目、国家重点研发计划项目、国家重大科技专项等,获得省部级科技进步奖7项、国家发明专利6 项和国家新药证书1 项。近年来在SciTransl Med、Nat Commu、Drug Metab Dispo、Anal Chem、J Chromatagr A 等学术刊物上发表系列论文,主编著作和教材4部。E‐mail:zengsu@zju.edu.cn.
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